Leptin eased hypothalamic amenorrhea in small trial: potential tx for infertility, anorexia nervosa.(News)

LISBON -- Recombinant human leptin appears to normalize many of the hormonal defects associated with hypothalamic amenorrhea, Dr. Christos S. Mantzoros reported at the 12th International Congress of Endocrinology.

The results of this landmark "proof of concept" study of eight women with hypothalamic amenorrhea and six controls suggest that leptin--a hormone secreted by adipocytes that regulates energy homeostasis--might represent a potential novel treatment for a range of neuroendocrine disorders, such as anorexia nervosa, infertility, and exercise-induced bone loss, said Dr. Mantzoros, director of the Human Nutrition Research Unit at Beth Israel Deaconess Medical Center, Boston.

If replicated by a placebo-controlled interventional study now underway in 80 subjects, the use of human recombinant leptin may prove preferable to current infertility treatment using pulsatile gonadotropin-releasing hormone therapy. Leptin is less expensive and better tolerated. It also improves bone density, which gonadotropin-releasing hormone does not.

"We are not at the stage of recommending treatment at this point, but I think that leptin could offer several therapeutic advantages," said Dr. Mantzoros, who is also with Harvard University.

In an open-label, prospective study that was funded by both the National Institutes of Health and Amgen, recombinant methionyl human leptin (r-metHuLeptin) was self-administered subcutaneously by eight otherwise healthy women aged 19-33 years who had secondary amenorrhea for a mean of 5.1 years due to increased exercise or low weight. None had eating disorders. The findings were published during the endocrinology congress (N. Engl. J. Med. 351[10]:987-97, 2004).

The recombinant leptin dosage was 0.08 mg/kg daily, with 40% of the total dose given at 8:00 a.m. and 60% given at 8:00 p.m. to mimic normal diurnal variation. If the patient ovulated, the study was concluded at 2 months. If not, the dose was increased to 0.2 mg/kg daily and continued for another month. Six similar women ...